Treatment of Male Infertility Edited by Jerald Bain, Wolf-Bernhard Schill and Luis Schwarzstein With 98 Figures Springer-Verlag Berlin Heidelberg New York 1982 Jerald Bain, M.D. Division of Endocrinology and Metabolism University of Toronto and Mount Sinai Hospital 600 University Avenue; Suites 639-640 Toronto, Ontario M5G IX5; Canada Prof. Dr. Wolf-B. Schill Dermatologische Klinik und Poliklinik der UniversiHit Munchen Frauenlobstr. 9-11 8000 Munchen 2, West Germany Dr. Luis Schwarzstein Grupo de Estudio en F ertilidad y Endocrinologia de Rosario Cordoba 1764 2000 Rosario (SF), Argentina ISBN-13: 978-3-642-68225-4 e-ISBN-13: 978-3-642-68223-0 DOl: 10.1007/978-3-642-68223-0 Library of Congress Cataloging in Publication Data. Main entry under title: Treatment of male infertility. Includes bibliographies and index. 1. Infertility, Male-Treatment. I. Bain, Jerald. II. Schill, W.-B. (Wolf-Bernhard), 1939-. III Schwarzstein, Luis, 1938-. [DNLM: 1. Sterility, Male-Therapy. WJ 709 T784] RC889.T73 616.6'92 82-3349 ISBN-13 :978-3-642-68225-4 (U.S.) AACR2 This work is subject to copyright. All rights are reserved, whether the whole or part of the material is concerned, specifically those of translation, reprint ing, re-use of illustrations, broadcasting, reproduction by photocopying ma chine or similar means, and storage in data banks. Under § 54 of the German Copyright Law where copies are made for other than private use a fee is payable to 'Verwertungsgesellschafi Wort', Munich. © Springer-Verlag Berlin Heidelberg 1982 Softcover reprint of the hardcover 1st edition 1982 The use ofregistered names, trademarks, etc. in this publication does not im ply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for gen eral use. 2121/3321 543210 Contents List of Contributors . xv Preface . XIX I. General Considerations Male Infertility: Problems in Assessing Response to Treatment (1. Bain) ...................... . II. Medical Treatment 1 Inflammation and Infection (c. R. D. Nahoum) 5 1.1 Inflammation of Male Accessory Sex Organs 5 1.1.1 Genital and Rectal Examination 5 1.1.2 Collection and Processing of the Prostatic Vesicular Fluid (PVF) 6 1.1.3 Cytological Examination ofPVF 7 1.1.3.1 Cellular Elements of the PVF 7 1.1.3.2 Quantitative Changes of the PVF Cells During Inflammation 8 1.1.3.3 Qualitative Changes of Epithelial Cells During Inflammation 11 1.1.3.4 Cellular Patterns of the Smears 11 1.1.4 Molecular Tracers of the Inflammatory Process 11 1.1.4.1 Immunoglobulins 12 1.1.4.2 C Factor of the Complement System 12 3 1.1.4.3 Albumin 14 1.1.4.4 aI-Antitrypsin 14 1.1.4.5 aI-Acid Glycoprotein 15 1.2 Infectious Male Adnexitis 15 1.2.1 General Considerations 15 1.2.2 Qualitative and Quantitative Data on Genital Infection in Infertile Patients 17 1.3 Secretory Function of Accesory Glands and Male Adnexitis 18 1.4 Treatment of Male Adnexitis 19 1.4.1 Introduction 19 1.4.2 Therapeutic Procedures 19 VI Contents 1.4.3 Follow-Up 26 1.5 Gaps in Our Knowledge 26 1.6 References 27 2 Clomiphene Citrate in the Treatment of Male Infertility (A. M. C. M. Schellen) 33 2.1 Testicular Control and Function 34 2.2 The Clomiphene Test 35 2.3 Clomiphene Citrate in Male Infertility 37 2.3.1 Clomiphene Citrate Therapy 37 2.3.2 Material and Methods 37 2.3.3 Review of Results Obtained with Clomid 40 2.4 Side and Secondary Effect of Clomiphene Citrate 41 2.5 Discussion 41 2.6 References 42 3 Tamoxifen (F. H. Comhaire) 45 3.1 Mode of Action 45 3.2 Patients 46 3.3 Results 47 3.3.1 Plasma Hormone Levels 47 3.3.1.1 Testosterone 47 3.3.1.2 Estradiol 47 3.3.1.3 Gonadotropins (LH and FSH) 48 3.3.2 Sperm Characteristics 49 3.3.2.1 Sperm Concentration 49 3.3.2.2 Sperm Motility 50 3.3.2.3 Sperm Morphology 50 3.3.3 Biochemical Composition of Seminal Plasma 50 3.3.4 Pregnancy 51 3.3.5 Side Effects 51 3.4 Conclusions 52 3.5 References 52 4 LHRH and Its Analogs in the Treatment of Idiopathic Normogonadotropic Oligozoospermia (L. Schwarzstein and N. Aparicio) 55 4.1 General Considerations 55 4.1.1 Hypothalamic Hormones 55 4.1.2 Male Infertility 56 4.2 Experience with LHRH and Its Analogs 57 4.2.1 Selection of Patients 57 4.2.2 Evaluation of Results 57 4.2.3 Experience with LHRH 58 4.2.4 D-Leucine6-LHRH-Ethylamide 61 4.2.5 D-Tryptophan6-LHRH 64 4.3 Conclusions 66 4.4 References 67 Contents VII 5 Hyperprolactinemia in Male Infertility: Treatment with Bromocriptine (E. del Pozo) 71 5.1 Control of PRL Release: The Role of Dopamine and Estrogens 71 5.2 Modification of PRL Secretion by Pharmacolog- ical Agents and Drug Interaction 73 5.3 Physiology and Physiopathology of PRL in Men 76 5.4 Incidence and Causes of Male Hyperprolactinemia 77 5.5 Biological and Biochemical Effect of Excessive PRL Secretion in Men 78 5.6 Bromocriptine Treatment of Male Hypogonadism 79 5.7 Conclusions 81 5.8 References 82 6 Gonadotropin Therapy in Male Infertility (S. J. Winters and P. Troen) 85 6.1 Gonadotropin Preparations 87 6.1.1 Pituitary Gonadotropins 87 6.1.2 hCG 87 6.1.3 FSH 87 6.2 Hypogonadotropic Hypogonadism 88 6.2.1 Treatment of Hypogonadotropics with hCG 89 6.2.2 Therapy with hMG 91 6.2.3 Therapy with hCG and hMG 91 6.3 Gonadotropin Treatment in Idiopathic Oligozoo- spermIa 94 6.4 Conclusions 97 6.5 References 98 7 Androgen Therapy in Hypogonadism and Infertility (E. Nieschlag and C. W. Freischem) 103 7.1 Mechanism of Testosterone Action 103 7.2 Pharmacology of Androgens 104 7.2.1 Free Testosterone 104 7.2.2 Parenteral Testosterone Esters 106 7.2.3 Testosterone U ndecanoa te 108 7.2.4 Synthetic Androgens 108 7.2.4.1 Methyltestosterone 108 7.2.4.2 Fluoxymesterone 109 7.2.4.3 Mesterolone 109 7.2.5 Testis Sicca and Testis Extracts 109 7.3 Clinical Application 109 7.3.1 Substitution of Endocrine Testicular Insufficiency 109 7.3.2 Idiopathic Delayed Puberty 110 7.3.3 Excessively Tall Boys 110 7.3.4 Androgens in Advanced Age 112 VIII Contents 7.3.5 Testosterone Rebound Therapy as Treatment of Male Infertility 112 7.4 References . 113 8 Mesterolone: a New Androgen for the Treatment of Male Infertility (B. N. Barwin) 117 8.l Properties of Mesterolone 117 8.2 Literature Review 118 8.3 Toleration and Function of the Liver 120 8.4 Conclusions 122 8.5 References 123 9 Kinin-Releasing Pancreatic Proteinase Kallikrein (W. B. Schill) 125 9.l Kallikrein-Kinin System 125 9.1.1 Biochemistry and Physiology 125 9.1.2 Reproductive Functions 127 9.2 Experimental Investigations 128 9.2.1 In Vitro Studies 128 9.2.2 Animal Studies 130 9.2.3 Biochemical and Endocrinological Studies in Men 130 9.3 Clinical Investigations and Application 131 9.3.l Systemic Kallikrein Treatment 131 9.3.1.1 Open Clinical Trials 132 9.3.1.2 Double Blind Studies 132 9.3.l.3 Routes of Administration and Side Effects 134 9.3.2 In Vitro Improvement of Human Semen 135 9.4 Conclusions 137 9.5 References 138 10 Treatment of Male Infertility with Nucleotides (G. F. Menchini-Fabris and M. Mariani) 143 1O.l Structure and Metabolism 143 10.2 Clinical Studies 145 10.2.1 Procedure 146 10.2.2 Treatment 148 10.3 Results 148 10.4 Conclusion 152 10.5 References 152 11 Immunological Infertility in Men: Clinical and Therapeutic Considerations (J. Friberg) 153 11.1 The Different Types of Sperm Antibodies Observed in Men 154 11.2 Antibody Nature of Sperm-Agglutinating and Sperm-Immobilizing Activities 155 1l.3 Causes of Sperm Antibody Production 156 Contents IX 11.4 The Significance of Sperm Antibodies in Men 157 11.5 Treatment of Men with Sperm Antibodies 159 11.5.1 Treatment of Men with Genital Infections .. 159 11.5.2 Surgical Treatment ........... 160 11.5.3 Sperm Washing and Intrauterine Inseminations 160 11.5.4 Immunosuppressive Treatment 161 11.5.4.1 Low-Dose Corticosteroids 161 11.5.4.2 High-Dose Corticosteroids 162 11.5.4.3 Azathioprine . . . . . . 164 11.5.5 The Testosterone Rebound Phenomenon and Sperm Antibodies 164 11.6 Conclusions 165 11.7 References . . . 166 12 Nonsurgical Treatment of Varicocele (M. P. P. de Castro) 169 12.1 Historical Background . 169 12.1.1 Diagnosis of Varicocele 170 12.1.2 Treatment of Varicocele 170 12.2 Transcatheter Sclerosis of the Spermatic Veins 171 12.3 Technique . . . . . . . 172 12.4 Observations in 88 Patients 172 12.5 Conclusions 176 12.6 References . . . . . . . 177 13 Retrograde Ejaculation (J. P. Collins) 179 13.1 Anatomy of the Male Urethra and Internal Genitalia .......... 179 13.2 Physiology of Ejaculation . . . . . 180 13.3 Etiology of Retrograde Ejaculation . 181 13.4 Diagnosis of Retrograde Ejaculation 183 13.5 Treatment of Retrograde Ejaculation 184 13.5.1 Retrieval of Semen ....... 184 13.5.1.1 Replacement of Bladder Urine with an Isotonic Alkaline Solution . . . . . . . . . . . .. 184 13.5.1.2 Systemic Alkalinization of the Urine . . . .. 185 13.5.1.3 Washing of Semen in Nutrient Alkaline Solution 185 13.5.2 Medication 186 13.5.3 Surgery 187 13.5.4 Miscellaneous 187 13.6 Conclusions 187 13.7 References . 188 14 Sexual Dysfunction in the Male (G. Kockott) 191 14.1 Definition ........ 191 14.1.1 Kinds of Sexual Dysfunction 191 14.1.1.1 Sexual Approach ..... 191 x Contents 14.1.1.2 Sexual Stimulation 191 14.1.1.3 Intromission and Pre orgasmic Coitus 192 14.1.1.4 Orgasm ........ . 192 14. 1. l.5 Postorgasmic Period . . . . . . . 193 14.l.2 Circumstances of Occurrence 193 14.2 Interviewing Technique and Differential Diagnosis Between "Organic" and "Psychogenic" Male Sexual Dysfunction 193 14.2.l Interviewing Technique 193 14.2.2 Differential Diagnosis 194 14.3 Etiology ..... . 195 14.3.l Organic Sexual Dysfunctions 195 14.3.1.1 Libido Disturbances . . 195 14.3.1.2 Erectile Impotence 197 14.3.1.3 Ejaculatory Disturbances . . 198 14.3.2 Psychogenic Sexual Dysfunctions 198 14.4 Therapy .......... . 199 14.4.l Therapy of Organic Sexual Dysfunctions 199 14.4.2 Therapy of Psychogenic Sexual Dysfunctions 199 14.4.2.1 Sexual Counseling 199 14.4.2.2 Partner Therapy .200 14.4.2.3 Psychoanalysis · 201 14.4.2.4 Behavior Therapy · 201 14.4.2.4.1 Therapy Concept and Format · 201 14.4.2.4.2 Initial Results . . .204 14.4.2.4.3 Follow-up Studies . . . . . .204 14.4.2.4.4 Conclusions ...... . · 205 14.5 Effect of Psychological Factors on the Production and Action of Spermatozoa .205 14.6 References . . . . . . . . . . . . . . . . .207 III. Surgical Treatment 15 Varicocele: Its Role in Male Infertility (H. Fenster and M. McLoughlin) .209 15.l Definition and Classification · 209 15.2 Pathogenesis and Etiology · 210 15.2.1 Metabolites .210 15.2.2 Heat ..... .211 15.2.3 Hormonal Factors · 212 15.2.4 Abnormal Gases · 212 15.2.5 Epididymal Factors · 212 15.3 Diagnosis · 213 15.4 Indications for Treatment · 214 15.5 Management · 215 15.5.l Surgical ...... . · 215 Contents XI 15.5.2 Medical · 217 15.6 Results · 217 15.7 Discussion and Conclusions · 218 15.8 References . . . . . . . · 219 16 Obstruction in the Male Reproductive Tract (L. V. Wagenknecht) · 221 l6.l Causes of Obstruction of the Male Reproductive Tract .222 16.1.1 Obstruction After Inflammation .222 16.1.2 Obstruction After Vasography .224 16.1.3 Aplasia or Hypoplasia of the Vas Deferens .226 16.1.4 Obstruction After Vasectomy · 227 16.1.5 Obstruction After Herniotomy .228 16.2 Therapy and Results · 228 l6.2.l Epididymovasostomy .228 16.2.2 Vasovasostomy · 234 16.2.3 Alloplastic Spermatocele · 237 16.3 Discussion and Conclusions .243 16.4 References .246 17 Hydrocele, Spermatocele, and Peyronie's Disease (A. Kelami) .249 17.l Hydrocele .249 17.1.1 Definition and Etiology .249 17.1.2 Symptoms .249 17.1.3 Diagnosis .250 17.1.4 Hydrocele and Testicular Tumors .250 17.1.5 Treatment · 251 17.2 Spermatocele · 251 17.2.l Definition and Etiology · 251 17.2.2 Symptoms · 252 17.2.3 Diagnosis · 253 17.2.4 Spermatocele and Epididymal Tumors · 253 17.2.5 Treatment .254 17.3 Peyronie's Disease (lnduratio Penis Plastica) .254 l7.3.l Definition and Etiology .254 17.3.2 Symptoms · 255 17.3.3 Diagnosis · 255 17.3.4 Nonsurgical Treatment · 255 17.3.5 Surgical Treatment · 255 l7.3.5.l Excision of the Plaques · 255 17.3.5.2 Implantation of Penile Prosthesis .257 17.4 Conclusion · 260 17.5 References .260